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Markus Schwaiger

Publications and source records attributed to Markus Schwaiger.

At least 109 records · Page 6Linked to original sources

Fluorodeoxyglucose-positron emission tomography in adenocarcinomas of the distal esophagus and cardia.

Adenocarcinomas of the esophagogastric junction (AEG) are now recognized as a separate tumor entity with increasing incidence. The aim of the present study was to evaluate whether positron emission tomography (PET) using the glucose analog F-18-fluorodeoxyglucose (FDG) can be used for metabolic characterization of this tumor type. Fifty-two patients with histologically proven, locally advanced AEG (distal esophagus, type I: n = 31; cardia, type II: n = 21) were studied by FDG-PET. None of the tumors had been previously treated. Findings of endoscopy (growth type), endoluminal ultrasound (uT, uN), computed tomography (cN, cranio-caudal extent, tumor thickness), histological evaluation (Lauren classification, tumor grade), anatomical classification, and survival were correlated with the results of FDG-PET. There was no correlation between FDG uptake and clinical stage, grade, Lauren classification, or survival. All AEG I tumors were visualized by FDG-PET with high contrast, whereas FDG uptake by five AEG II tumors (24%) did not differ from background activity. In a quantitative analysis, mean FDG uptake of AEG I tumors was 1.6 times higher than that of AEG II tumors ( p = 0.0005). PET can be used to visualize type I adenocarcinomas of the esophagogastric junction (AEG I). In AEG II tumors, however, the use of FDG-PET appears to be limited. The significantly higher FDG uptake of AEG I tumors compared to AEG II tumors suggests that these two tumor types differ in glucose utilization. This finding strengthens the hypothesis that AEG I and AEG II are two different tumor entities.

Adenocarcinoma↗

Therapy-dependent influence of time-to-treatment interval on myocardial salvage in patients with acute myocardial infarction treated with coronary artery stenting or thrombolysis.

BACKGROUND: The relationship between myocardial salvage and time-to-treatment interval in patients with acute myocardial infarction (AMI) treated with coronary artery stenting or thrombolysis has not been studied. METHODS AND RESULTS: This study analyzed 264 patients with AMI randomized to coronary stenting (133 patients) or thrombolysis (131 patients) in the setting of 2 randomized trials. Patients were divided into the following 3 groups defined by tertiles of the time-to-treatment interval: lower tertile (<165 minutes), middle tertile (165 to 280 minutes), and upper tertile (>280 minutes). Paired scintigraphic examinations were performed to obtain salvage index, which was the primary end point of the study. In the group with thrombolysis, the salvage index (median [25th; 75th] percentile) was 0.45 (0.16; 0.83) in the lower, 0.29 (0.17; 0.48) in the middle, and 0.20 (0.04; 0.46) in the upper tertile (P=0.03). In the group with stenting, the salvage index was 0.56 (0.49; 0.75) in the lower, 0.57 (0.36; 0.73) in the middle, and 0.57 (0.32; 0.75) in the upper tertile (P=0.59). In patients treated with stenting, the salvage index was greater than in patients treated with thrombolysis in the lower (0.56 versus 0.45, P=0.09), middle (0.57 versus 0.29, P=0.0003), and upper (0.57 versus 0.20, P=0.0005) tertiles of the time-to-treatment interval. CONCLUSIONS: The influence of the time-to-treatment interval on the myocardial salvage in patients with AMI depends on the type of reperfusion therapy. Coronary artery stenting was superior to thrombolysis independent of the time-to-treatment intervals, and the difference in benefit increased with more prolonged time from symptom onset.

Aged↗

Validation of a method for automatic image fusion (BrainLAB System) of CT data and 11C-methionine-PET data for stereotactic radiotherapy using a LINAC: first clinical experience.

PURPOSE: (a) To implement a fully automatic method to integrate (11)C-methionine positron emission tomography (MET-PET) data into stereotactic radiation treatment planning using the commercially available BrainLAB System, by means of CT/MET-PET image fusion. (b) To validate the fully automatic CT/MET-PET image fusion technique with respect to accuracy and robustness. (c) To give a short glance at the clinical consequences for patients with brain tumors. METHODS AND MATERIALS: In 12 patients with brain tumors (9 meningeomas, 3 gliomas), CT, MRI, and MET-PET were performed for stereotactic fractionated radiation treatment planning. The CT and MET-PET investigations were performed using a relocatable mask for head fixation. Fifteen external reference markers (5 on each lateral and 5 on the frontal localizer plate) that could be identified in CT and MET-PET were applied on the stereotactic localizer frame; the marker positions were exactly defined for both investigations. The MRI/CT fusion was done completely automatically. The CT/MET-PET fusion was performed using two different methods: The gold standard was the CT/PET fusion based on the reference markers, and the test method was the automatic, intensity-based CT/PET fusion, independent of the external markers. The markers visible on CT and transmission PET were matched using a point-to-line matching algorithm. To quantify the amount of misregistration, the two fusion methods were compared by calculating the mean value of deviation between corresponding points inside a cubic volume of interest of > or =512 cm(3) defined within the cranial cavity. The gross tumor volume (CT/MRI) outlined on CT and T1-MRI with contrast medium was compared with the gross tumor volume (PET) defined in the reoriented MET-PET data sets. The clinical impact of MET-PET in tumor volume definition for stereotactic radiotherapy will be discussed. RESULTS: The fully automatic integration of MET-PET into stereotactic radiation treatment planning was successfully realized in all patients investigated. Mean deviation of the intensity-based automatic CT/PET fusion compared with the external marker-based gold standard was 2.4 mm; the standard deviation was 0.5. The algorithm's robustness was evaluated, and the discrepancy of fusion results due to different initial image alignments was determined to be below 1 mm inside the test volume of interest. In patients with meningiomas and gliomas, MET-PET was shown to deliver additional information concerning tumor extension. CONCLUSION: The precision of the automatic CT/PET image fusion was high. A mean deviation of 2.4 mm is acceptable, considering that it is approximately equal to the pixel size of the PET data sets. MET-PET improves target volume definition for stereotactic fractionated radiotherapy of meningiomas and gliomas.

Adult↗

Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use.

PURPOSE: To prospectively evaluate the use of positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) to predict response to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC scheduled to undergo platinum-based chemotherapy were eligible for this study. Patients were studied by FDG-PET before and after the first cycle of therapy. Based on previous studies, a reduction of tumor FDG uptake by more than 20% as assessed by standardized uptake values (SUV) was used as a criterion for a metabolic response. Furthermore, changes in tumor SUVs were compared with changes in FDG net-influx constants (Ki) and tumor/muscle ratios (t/m). RESULTS: Fifty-seven patients were included in the study. There was a close correlation between metabolic response and best response to therapy according to Response Evaluation Criteria in Solid Tumors (P <.0001; sensitivity and specificity for prediction of best response, 95% and 74%, respectively). Median time to progression and overall survival were significantly longer for metabolic responders than for metabolic nonresponders (163 v 54 days and 252 days v 151 days, respectively). Similar results were obtained when Ki was used to assess tumor glucose use, whereas changes in t/m showed considerable overlap between responding and nonresponding tumors. CONCLUSION: In NSCLC, reduction of metabolic activity after one cycle of chemotherapy is closely correlated with final outcome of therapy. Using metabolic response as an end point may shorten the duration of phase II studies evaluating new cytotoxic drugs and may decrease the morbidity and costs of therapy in nonresponding patients.

Aged↗

Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study.

A high percentage of patients with mild cognitive impairment (MCI) develop clinical dementia of the Alzheimer type (AD) within 1 year. The aim of this longitudinal study was to identify characteristic patterns of cerebral metabolism at baseline in patients converting from MCI to AD, and to evaluate the changes in these patterns over time. Baseline and follow-up examinations after 1 year were performed in 22 MCI patients (12 males, 10 females, aged 69.8+/-5.8 years); these examinations included neuropsychological testing, structural cranial magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography (PET) evaluation of relative cerebral glucose metabolic rate (rCMRglc). Individual PET scans were stereotactically normalised with NEUROSTAT software (Univ. of Michigan, Ann Arbor, USA). Subsequently, statistical comparison of PET data with an age-matched healthy control population and between patient subgroups was performed using SPM 99 (Wellcome Dept. of Neuroimaging Sciences, London, UK). After 1 year, eight patients (36%) had developed probable AD (referred to as MCI(AD)), whereas 12 (55%) were still classified as having stable MCI (referred to as MCI(MCI)). Compared with the healthy control group, a reduced rCMRglc in AD-typical regions, including the temporoparietal and posterior cingulate cortex, was detected at baseline in patients with MCI(AD). Abnormalities in the posterior cingulate cortex reached significance even in comparison with the MCI(MCI) group. After 1 year, MCI(AD) patients demonstrated an additional bilateral reduction of rCMRglc in prefrontal areas, along with a further progression of the abnormalities in the parietal and posterior cingulate cortex. No such changes were observed in the MCI(MCI) group. In patients with MCI, characteristic cerebral metabolic differences can be delineated at the time of initial presentation, which helps to define prognostic subgroups. A newly emerging reduction of rCMRglc in prefrontal cortical areas is associated with the transition from MCI to AD.

Aged↗

Thrombolysis in myocardial infarction myocardial perfusion grade in angiography correlates with myocardial salvage in patients with acute myocardial infarction treated with stenting or thrombolysis.

OBJECTIVES: We sought to assess the relationship between the Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion (TMP) grade and myocardial salvage as well as the usefulness of TMP grade in comparing two different reperfusion strategies. BACKGROUND: The angiographic index of TMP grade correlates with infarct size and mortality after thrombolysis for acute myocardial infarction (AMI). Its relationship to myocardial salvage and its usefulness in comparing different reperfusion strategies are not known. METHODS: We analyzed the TMP grade on angiograms obtained at one to two weeks after treatment in 267 patients enrolled in two randomized trials that compared stenting with thrombolysis in AMI. Patients were classified into two groups: 159 patients with TMP grade 2/3 and 108 patients with TMP grade 0/1. Two scintigraphic studies were performed: before and one to two weeks after reperfusion. The salvage index was calculated as the proportion of the area at risk salvaged by reperfusion. RESULTS: Patients with TMP grade 2/3 had a higher salvage index (0.49 +/- 0.42 vs. 0.34 +/- 0.49, p = 0.01), a smaller final infarct size (15.4 +/- 15.5% vs. 22.1 +/- 16.2% of the left ventricle, p = 0.001), and a trend toward lower one-year mortality (3.8% vs. 8.3%, p = 0.11) than patients with TMP grade 0/1. The relationship between TMP and salvage index was independent of the form of reperfusion therapy. The proportion of patients with TMP grade 2/3 was significantly higher after stenting than after thrombolysis (70.9% vs. 48.1%, p = 0.001). CONCLUSIONS: These findings show that the TMP grade is a useful marker of the degree of myocardial salvage achieved with reperfusion and a sensitive indicator of the efficacy of reperfusion strategies in patients with AMI.

Abciximab↗

Predictive value of basal C-reactive protein levels for myocardial salvage in patients with acute myocardial infarction is dependent on the type of reperfusion treatment.

AIMS: To evaluate whether C-reactive protein (CRP) levels on admission are predictive of myocardial salvage achieved with different reperfusion strategies in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Patients with AMI treated with stenting plus abciximab (n=125) and thrombolysis alone (n=54) or with abciximab (n=71) were prospectively studied. CRP levels were measured by a high sensitivity assay. The threshold of the upper quartile (12 mg/l) was used to divide patients into two groups: 60 patients with high CRP (>12 mg/l) and 190 patients with low CRP (< or =12 mg/l). Myocardial salvage was measured by technetium (Tc)-99(m)sestamibi scintigraphy. Patients in the high CRP group had a significantly lower salvage index (0.35+/-0.42 vs 0.48+/-0.34, p=0.01) and higher 18-month mortality (11.7 vs 3.2%, p=0.03) compared to those in the low CRP group. While basal CRP was not related to myocardial salvage in patients treated with stenting plus abciximab (p=0.89) or thrombolysis plus abciximab (p=0.43), a high CRP on admission was associated with a significantly lower salvage index (0.09+/-0.48 vs 0.42+/-0.37 in the low CRP group, p=0.006) among patients treated with thrombolysis alone. CONCLUSION: CRP levels on admission may predict the efficacy of reperfusion in patients with AMI. The predictive ability is dependent on the form of reperfusion therapy.

Abciximab↗

Cardiac oxidative metabolism, function, and metabolic performance in mild hyperthyroidism: a noninvasive study using positron emission tomography and magnetic resonance imaging.

Using noninvasive imaging, we have previously demonstrated that myocardial efficiency is impaired in hypothyroidism and improves after establishing euthyroid conditions. Little is known about the effects of abnormally elevated thyroid hormone exposure on cardiac metabolic performance. We studied 10 patients without evidence of heart disease in mild hyperthyroidism, and after therapy under euthyroid conditions. Cardiac oxidative metabolism was quantified by positron emission tomography with [(11)C]acetate. Left ventricular geometry was determined by cine magnetic resonance imaging. Myocardial efficiency, defined by the relation between work and oxygen consumption, was estimated using the work metabolic index [WMI = stroke volume * systolic blood pressure * heart rate/(oxidative metabolism * ventricular mass)]. In hyperthyroidism, heart rate and cardiac output were expectedly higher. Peripheral vascular resistance was reduced. Differences of blood pressure, stroke volume, and ventricular mass were not observed. Oxidative metabolism was significantly higher, but WMI was not different from the euthyroid state. In summary, while improvement of efficiency through thyroid hormone substitution was observed previously in hypothyroidism, our data in mild hyperthyroidism suggest an increase of oxygen consumption, paralleled by an increase of work. Thus, moderately elevated thyroid hormone levels neither result in further increase nor in reduction of cardiac metabolic performance.

Acetates↗

FDG PET imaging of locally advanced gastric carcinomas: correlation with endoscopic and histopathological findings.

Gastric cancer carries a poor prognosis and is the second most frequent cause of cancer-related death worldwide. In spite of the clinical importance of this tumour entity, only a few fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) studies have been published on gastric carcinomas. The aim of this study was to characterise the FDG uptake of gastric carcinomas by relating it to the histopathological properties of the tumours. Within this context, we focussed particularly on the microscopic growth type according to Lauren since our preliminary observations indicated low FDG accumulation in the non-intestinal growth type compared with the intestinal type. Forty patients with locally advanced gastric carcinomas and ten control subjects were studied by FDG PET (300 MBq i.v., emission scan: 40 min p.i., one bed position, measured transmission, filtered back-projection). Detectability of the tumours was qualitatively assessed by two independent observers. For quantitative analysis the regional tumour uptake was measured by standardised uptake values (SUV normalised to the body surface area) using a region of interest technique. Qualitative and quantitative analyses were performed with respect to the microscopic growth type according to Lauren (intestinal type vs non-intestinal type). Other histopathological characteristics were also assessed: mucus content, grading, tumour extension and tumour location. In 36 patients the survival rates were compared for detectable vs non-detectable tumours and for tumour FDG uptake above and below the median. Only 24 of the 40 locally advanced gastric carcinomas (60%) were detected by FDG PET. The detection rate for tumours of the intestinal type was significantly higher than that for tumours of the non-intestinal type (83% vs 41%, P=0.01). Only 2/18 intestinal type tumours contained extracellular or intracellular mucus whereas 17/22 non-intestinal tumours did so (P<0.01). The mean SUV was significantly different between the intestinal type and the non-intestinal type (6.7+/-3.4 vs 4.8+/-2.8, P=0.03), between non-mucus-containing tumours and mucus-containing tumours (7.2+/-3.2 vs 3.9+/-2.1, P<0.01) and between grade 2 tumours and grade 3 tumours (7.4+/-2.3 vs 5.2+/-3.3, P=0.02). The survival rate was not significantly different in patients with detectable tumours on FDG PET and patients with non-detectable tumours (P=0.85). It is concluded that advanced malignant tumours with a poor prognosis may show low FDG uptake due to special histopathological characteristics. The overall low detection rate of gastric carcinomas is attributable to the frequent occurrence of diffusely growing and mucus-containing tumour types. This may limit the value of FDG PET for diagnosis and therapy monitoring in patients with gastric carcinomas. Furthermore, the intensity of tumour FDG uptake is not predictive of survival in gastric carcinomas.

Fluorodeoxyglucose F18↗

Implications of IMT-SPECT for postoperative radiotherapy planning in patients with gliomas.

PURPOSE: Using MRI, residual tumor cannot be differentiated from nonspecific postoperative changes in patients with brain gliomas after surgical resection. The goal of this study was to analyze the value of 123I-alpha-methyl-tyrosine-single photon emission CT (IMT-SPECT) in radiotherapy planning of patients with brain gliomas after surgical resection. METHODS AND MATERIALS: In 66 patients with surgically resected brain gliomas (33 glioblastomas, 20 anaplastic astrocytomas, 7 anaplastic oligodendrogliomas, and 6 low-grade astrocytomas), IMT-SPECT and MRI were performed for radiotherapy planning. On the MRI/IMT-SPECT fusion images, the volume with IMT uptake was compared with the volume of the hyperintensity areas of T(2)-weighted MRI and with the volume of contrast enhancement on T(1)-weighted MRI. The regions with IMT uptake and/or MRI changes (composite Vol-MRI/IMT), regions with overlay of IMT uptake and MRI changes (common Vol-MRI/IMT), area with IMT uptake without MRI changes (increase Vol-MRI/IMT), and area with only MRI changes (Vol-MRI minus IMT) were analyzed separately. The planning target volume and boost volume defined using MRI information alone was compared with the planning target volume and boost volume defined by also using the SPECT information. RESULTS: Focally increased IMT uptake was observed in 25 (38%) of 66 patients, contrast enhancement on MRI was outlined in 59 (89%) of 66 patients, and hyperintensity areas on T(2)-weighted MRI were found in all 66 investigated patients. The mean composite Vol-T(2)/IMT was 73 cm(3). The relative increase Vol-T(2)/IMT, mean relative common Vol-T(2)/IMT, and mean relative Vol-T(2) minus IMT was 4%, 6%, and 90% of the composite Vol-T(2)/IMT, respectively. The mean composite Vol-T(1)/IMT was 14 cm(3) and the mean relative increase Vol-T(1)/IMT, mean relative common Vol-T(1)/IMT, and mean relative Vol-T(1) minus IMT was 21%, 4%, and 64% of the mean composite Vol-T(1)/IMT, respectively. In 19 (29%) of 66 patients, the focal IMT uptake was located outside the MRI changes. In this subgroup, the mean residual volume defined by focal IMT uptake in MRI/IMT-SPECT images, mean Vol-T(1), and mean Vol-T(2) was 19 cm(3), 10 cm(3), and 70 cm(3), respectively. The mean relative increase T(2)/IMT was 14% and T(1)/IMT was 61%. In this subgroup, the additional information of SPECT led to an increase in boost volume (mean relative increase BV-IMT) by 20%. CONCLUSION: In patients with surgically resected brain gliomas, the size and location of residual IMT uptake differs considerably from the abnormalities found on postoperative MRI. Because of the known high specificity of IMT uptake for tumor tissue, the findings on IMT-SPECT may significantly modify the target volumes for radiotherapy planning. This will help to focus the high irradiation dose on the tumor area and to spare normal brain tissue.

Adolescent↗

Dysregulation of coronary microvascular reactivity in asymptomatic patients with type 2 diabetes mellitus.

In diabetic patients, a number of studies have suggested an impairment of vascular reactivity in response to vasodilatory stimuli. The pattern of dysregulation at the coronary microcirculatory level, however, has not been clearly defined. Thus, it was the aim of this study to characterise coronary microvascular function non-invasively in a homogeneous group of asymptomatic type 2 diabetic patients. In 46 patients with type 2 diabetes, myocardial blood flow (MBF) was quantified at baseline, in response to cold pressor test (CPT) and during adenosine-mediated vasodilation using positron emission tomography and nitrogen-13 ammonia. None of the patients had been treated with insulin, and none had symptoms of cardiac disease. Decreased MBF during CPT, indicating microvascular dysregulation, was observed in 16 patients (CPT-), while 30 patients demonstrated increased MBF during CPT (CPT+). Response to CPT was mildly, but significantly correlated with response to adenosine ( r=0.44, P=0.0035). There was no difference in HbA1c, serum lipid levels or serum endothelial markers between the groups. Microvascular dysregulation in the CPT- group was associated with elevated baseline MBF ( P<0.0001), reduced baseline vascular resistance ( P=0.0026) and an abnormal increase in resistance during CPT ( P=0.0002). In conclusion, coronary microvascular dysregulation is present in approximately one-third of asymptomatic, non-insulin-treated type 2 diabetic patients. Elevated baseline blood flow and reduced microvascular resistance at rest are characteristics of this dysregulation. These data suggest a state of activation of endothelial-dependent vasodilation at baseline which appears to limit the flow response to stress conditions.

Adenosine↗

More accurate quantification of pulmonary blood flow by magnetic resonance imaging than by lung perfusion scintigraphy in patients with fontan circulation.

BACKGROUND: Quantitative evaluation of pulmonary perfusion using lung perfusion scintigraphy in patients with atriopulmonary anastomosis (APA) or total cavopulmonary connection (TCPC) or partial cavopulmonary connection (PCPC) is difficult because of preferential draining of the venae cavae to one lung. Scintigraphy is the gold standard. Phase-velocity MRI (PV-MRI) is a new technique for determining pulmonary perfusion. The aim of this study was therefore to determine whether PV-MRI is more accurate than scintigraphy for quantitative evaluation of pulmonary perfusion ratios in patients with APA, TCPC, or PCPC. METHODS AND RESULTS: We studied 15 patients with APA, TCPC, or PCPC (16+/-7 years old, 4 female). Twelve patients (15+/-8 years old, 3 female) with a single pulmonary blood source supplied by a subpulmonary ventricle, ensuring complete mixing of the radioactive tracer before entering the pulmonary circulation, served as controls. Pulmonary scintigraphy and PV-MRI were performed in all patients. Bland-Altman analysis showed a clinically unacceptable difference of 7.1% right pulmonary blood flow (27.2% upper and -13.0% lower limit of agreement) between the two methods in the study group. The two methods agreed excellently in the control group (difference, 1.6%; 4.0% upper and -7.2% lower limit of agreement), showing that the bad agreement in the study group was caused by the problems encountered using pulmonary scintigraphy in patients with APA, TCPC, or PCPC. CONCLUSIONS: Because of preferential caval flow into either lung, PV-MRI is more accurate for evaluating pulmonary perfusion ratios than lung perfusion scintigraphy in patients with Fontan-like circulation.

Adolescent↗

Clinical determinants of ventricular sympathetic reinnervation after orthotopic heart transplantation.

BACKGROUND: It has been demonstrated that ventricular sympathetic reinnervation after cardiac transplantation improves exercise performance. The extent of reinnervation increases with time but is variable. Little is known about other influencing factors. METHODS AND RESULTS: Seventy-seven nonrejecting transplant recipients were cross-sectionally studied by PET with the catecholamine analogue C-11 hydroxyephedrine at 4.8+/-3.5 years after transplantation. Results were compared with history-derived parameters related to recipient's clinical course before, during, and after surgery; donor characteristics; and immunogenetics. Partial reinnervation was observed in 52 patients (extent, 21+/-16% of left ventricle). Complete denervation was found in 25 patients at various times after transplantation. Reinnervation extent correlated with time after surgery (r=0.387; P<0.001) but also inversely with donor age (r=-0.309, P=0.006) and recipient age (r=-0.243, P=0.032). Maximal hydroxyephedrine retention correlated inversely with frequency of rejection episodes (r=-0.267, P=0.019), was reduced when aortic complications occurred perioperatively (9 patients), and correlated inversely with aortic cross-clamp time (r=-0.331, P=0.006). Other parameters were not associated with reinnervation. Patients were surveyed for clinical complications over >12 months after PET (until 7.3+/-4.2 years after transplantation), but significant effects of reinnervation on outcome were not observed. CONCLUSIONS: The present data suggest that sympathetic reinnervation after cardiac transplantation is not simply a function of time. Reinnervation is more likely with young age, fast and uncomplicated surgery, and low rejection frequency. Despite few effects on prognosis in otherwise healthy recipients, improved understanding of clinical determinants may contribute to enhance allograft reinnervation and thereby augment exercise capacity in the future.

Adult↗

Biodistribution and kinetics of (131)I-labelled anti-CD20 MAB IDEC-C2B8 (rituximab) in relapsed non-Hodgkin's lymphoma.

The native chimeric human-mouse anti-CD20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the distribution and pharmacokinetics of iodine-131 labelled rituximab in humans for radioimmunotherapy of relapsed CD20-positive NHL. Thirty-five patients with relapsed NHL were administered 20-40 mg rituximab labelled with 250 MBq (131)I. Biodistribution was determined by the gamma camera whole-body scans, whole-body probe measurements and the analysis of serial blood and urine samples. Dosimetry was performed using the MIRDOSE 3 program. Antibody administration was well tolerated. The whole-body activity showed a mono-exponential decrease with a wide range of effective half-lives, the mean value (88 h) being significantly longer than the half-life of its murine counterpart, tositumomab. This led to appropriately higher dose factors for the whole body and organs. Activity was excreted mainly through the kidneys. Normal organs showed decreasing ratios of organ to whole-body activity over time, whereas the tumour tissue presented different kinetics, with increasing ratios of tumour to whole-body activity as evidence for specific antibody binding. It is concluded that (131)I-labelled rituximab is suitable for pretherapeutic dosimetry. Due to the wide range of whole-body and organ dose factors, individual dosimetry is necessary for radioimmunotherapy with (131)I-labelled rituximab. The therapeutic activities of (131)I-labelled rituximab required to deliver similar doses should be lower than those of its murine counterpart.

Adult↗

Early resolution of ST-segment elevation correlates with myocardial salvage assessed by Tc-99m sestamibi scintigraphy in patients with acute myocardial infarction after mechanical or thrombolytic reperfusion therapy.

BACKGROUND: Early resolution of ST-segment elevation is an indicator of final infarct size and clinical outcomes. Whether this correlation is an expression of initial infarct characteristics or degree of myocardial salvage achieved with reperfusion therapy is unclear. METHODS AND RESULTS: We prospectively included 243 patients with acute myocardial infarction (AMI) treated with either coronary stenting (122 patients) or thrombolysis (121 patients). Serial 12-lead electrocardiograms (ECG) were performed at baseline and 90 minutes after initiation of therapy. ST-segment resolution was defined as complete (> or =70%), partial (<70% to 30%), or no resolution (<30%). Paired technetium-99m sestamibi scintigraphic studies were performed to calculate the initial perfusion defect, final infarct size, and the proportion of initial defect salvaged with reperfusion (salvage index). ST-segment resolution correlated significantly with salvage index (P=0.008), final infarct size (P<0.001), and 6-month mortality (P=0.03). In the groups with complete, partial, and no resolution, salvage index was 0.54+/-0.32, 0.39+/-0.36, and 0.33+/-0.60; final infarct size was 12.5+/-12.0%, 20.0+/-13.9%, and 22.7+/-19.4% of the left ventricle; 6-month mortality was 2.4%, 6.2%, and 12.8%, respectively. After adjustment for baseline characteristics, ST-segment resolution was the second strongest predictor of salvage index (P=0.007) after the type of reperfusion, stenting, or thrombolysis (P=0.001); it was greater after stenting than after thrombolysis (P<0.001). CONCLUSION: Early resolution of ST-segment elevation in surface ECG correlates with myocardial salvage as assessed by scintigraphy in patients with AMI after reperfusion therapy. These data provide an explanation for the favorable prognostic value of the ST-segment resolution and support the use of this parameter to compare the efficacy of different reperfusion strategies.

Electrocardiography↗